Cardiac disease is the leading cause of maternal mortality during pregnancy in high-resource countries.
A 31-year-old woman had an ST-elevated myocardial infarction (STEMI) at 16 gestational weeks. The patient received three coronary drug-eluting stents followed by dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. An elective caesarean delivery was performed under general anesthesia at 37+1 gestational weeks. Due to subnormal response to clopidogrel, administration was paused only 24 h perioperatively without bridging with tirofiban because of the slightly increased risk of stent thrombosis in clopidogrel nonresponders. There was no postoperative bleeding.
There is a lack of evidence-based guidelines regarding the management of acute myocardial infarction (AMI) during pregnancy; thus, delivery should be performed in a tertiary center with a multidisciplinary approach.
Cardiac disease is the leading cause of maternal mortality during pregnancy in high-resource countries . Although acute myocardial infarction (AMI) is very rare among women of child-bearing age, an increasing number of cases is expected due to the trend of increasing maternal age as a consequence of delaying maternity. Interdisciplinary management should be carried out in these high-risk pregnancies by obstetricians, cardiologists, anesthesiologists, hematologists and neonatologists to ensure that the best therapeutic plan is put into place. There is a lack of data regarding the management of AMI during pregnancy and the optimal delivery mode.
A 31-year-old woman, gravida 1 para 1, was referred to our tertiary university perinatal center at 20+6 gestational weeks so that further interdisciplinary management of her pregnancy and delivery could be planned. During the pregnancy, she had presented with intermediate substernal chest pain, dizziness, and dyspnea due to acute myocardial infarction at 15+6 gestational weeks to the chest pain clinic. Electrocardiogram revealed normal sinus rhythm, heart rate of 70 bpm and ST segment elevation. The patient was hemodynamically stable. Blood pressure was 120/85 mm Hg. Laboratory findings showed elevated troponin T, creatine kinase and creatine kinase-MB levels. The cause of AMI in this young patient remained unclear. There were moderate risk factors, such as hypothyreosis under medical substitution, hyperlipidemia with triglycerides of 240 mg/dL, moderately elevated low-density lipoprotein (LDL) of 120 mg/dL and low nicotine use (4 Py) before pregnancy. Testing was negative for increased lipoprotein A, thrombophilia and antiphospholipid syndrome, which are associated with thrombosis.
Angiography revealed total occlusion of the proximal left anterior descending artery (LAD) and nonstenotic atherosclerosis of the circumflex artery. The ramus intermedius had 60% stenosis. The right coronary artery had 40%–50% stenosis. Two stents were implanted: the Absorb® stent (2.5 × 18 mm) in the LAD/ramus diagonalis and the Xience Pro® stent (2.5 × 15 mm) in the LAD. Because of a small dissection caused during the intervention, the patient also underwent implantation of a third drug-eluting stent (Xience Pro®, 4.0 × 12 mm) in the main stem of the left coronary main artery (Absorb und Xience Pro – Abbott Vascular GmbH&Co, Wiesbaden, Germany).
Dual antiplatelet therapy (DAPT) was indicated for 12 months after drug-eluting stent implantation, followed by indefinite low-dose aspirin therapy. Because of the lack of evidence regarding prasugrel during pregnancy, our patient received 75 mg of clopidogrel 1–0–0 with 100 mg of aspirin 1–0–0 and 47.5 mg of metoprolol 1–0–1. Follow-up was uneventful, and the patient was discharged home for 2 weeks of rehabilitation after AMI.
The patient’s next presentation at our clinic was at 20+6 gestational weeks for further management planning. Second-trimester screening showed a vital fetus with normal growth and flow parameters without any malformation.
An interdisciplinary team of obstetricians, cardiologists, neonatologists, anaesthesiologists and hematologists decided with the patient and her partner to proceed with elective caesarean section at 37 weeks of gestation under general anesthesia.
There was some concern because the patient was receiving DAPT and ran the risk of epidural hematoma after epidural anesthesia. However, stopping DAPT before birth would have carried a high risk for stent thrombosis.
Hospitalization and discontinuation of clopidogrel was planned at 36+0 gestational weeks, 1 week before the planned caesarean delivery, with continuation of aspirin. A Multiplate® analysis performed 10 days previously revealed a subnormal response to clopidogrel (49 U, normal range 57–113 U) and a full response to aspirin. Therefore, clopidogrel was paused 24 h perioperatively without bridging with tirofiban as planned initially because of the slightly increased risk of stent thrombosis in clopidogrel nonresponders.
Elective caesarean delivery was performed at 37+1 gestational weeks under general anesthesia, as this was the wish of the patient, and to avoid the risk of epidural hematoma. A male infant, weighing 3300 g, with a length of 51 cm, APGAR scores of 9/10/10 and postpartal umbilical artery pH of 7.27, was delivered without complications. A double-layer uterotomy closure was performed to minimize the risk of postoperative bleeding. There was no increased blood loss, with 500 mL estimated. There was no prophylactic administration of platelets. The postoperative course of the patient was unremarkable, without further bleeding or any cardiac problems. She was transferred for monitoring to the cardiac intensive care unit for 12 h. Postoperative hemoglobin content was 10.2 g/dL (preoperative 11.1 g/dL) and platelet count remained stable.
Eight hours after caesarean section, prasugrel instead of clopidogrel was administered, with a loading dose of 30 mg. Afterwards, she was restarted on a regimen of 10 mg of prasugrel 1–0–0, 100 mg of aspirin 1–0–0 and 47.5 mg of metoprolol 2–0–2 to prevent further stent thrombosis. Mother and infant were discharged home on postoperative day 4 in good health.
In the UK, AMI and chronic ischemic heart disease are associated with one-fifth of maternal mortalities due to cardiac disease (i.e. 2.3 per 100,000 pregnant women) . The incidence of acquired cardiac disease in pregnancy is likely to rise due to current lifestyle factors in high-resource countries. Maternal age is one of the leading risk factors. Every year, the odds of AMI increase by 30% . Pregnancy itself is also known to be a risk factor, increasing the likelihood of AMI by 3- to 4-fold because of physiological cardiovascular changes, with hypercoagulability during pregnancy and the increased workload of the maternal heart caused by increased blood volume, heart rate and cardiac output .
There are limited data regarding the diagnosis and management of AMI in pregnancy. Counseling of these patients remains difficult because standard treatment with beta-blockers and angiotensin-converting enzyme inhibitors is pregnancy category C or D and there is little experience during pregnancy with newer treatments such as coronary artery stenting, clopidogrel and glycoprotein IIb/IIIa inhibitors. Wilson et al. performed Pubmed and Cochrane database reviews of ischemic heart disease in women of childbearing age and found that most knowledge is based on case reports; thus, more relevant data is needed .
The appropriate medication after AMI and stenting during pregnancy is still under debate. The current recommendation is DAPT with aspirin and clopidogrel for 12 months. Trials have shown that DAPT, mostly with aspirin and clopidogrel, reduces the risk of stent thrombosis , death, myocardial infarction and/or stroke compared to a short-term therapy of 4 weeks .
Low-dose aspirin is prophylactically used in women with a high risk of preeclampsia during pregnancy .
Clopidogrel is an irreversible platelet inhibitor, and full recovery of platelet function is not recovered until 7–8 days after discontinuation. Its use within 5 days of surgery has been shown to be associated with excess major bleeding. The addition of clopidogrel to aspirin significantly increases bleeding time .
Literature of reported cases with clopidogrel use in pregnancy and perioperative bleeding risk during caesaerean section is rare.
Myers et al. described a case of a woman who had an AMI with stenting 2 months before conception. Clopidogrel was given without aspirin throughout the pregnancy and urgent caesarean section was performed under general anesthesia. Prophylactic platelets were administered. Postoperative bleeding occurred, with hemoglobin decreasing from 9.2 g/dL to 5.6 g/dL .
Unlike our case, where we did not administer prophylactic blood cells and there was no perioperative bleeding after clopidogrel, the patient experienced the complication of clopidogrel as an irreversible antiplatelet inhibitor. In our case, the decision to continue clopidogrel medication until 1 day before caesarean section without bridging with tirofiban was based on the fact that several Multiplate® tests revealed that she had only a slight response to clopidogrel, and there is a slight risk of stent thrombosis or perioperative bleeding in a nonresponder.
Cuthill et al. reported a similar case of a coronary artery disease at 18 gestational weeks followed by an insertion of a drug-eluting stent and DAPT with low-dose aspirin and clopidogrel. Caesarean section was performed under general anesthesia at 35 gestational weeks. Clopidogrel and aspirin were given until 1 day before surgery. There was no prophylactic platelet administration. Surgery was uncomplicated, but there was postoperative bleeding with a drop in hemoglobin from 11.3 g/dL to 6.3 g/dL . In the two previous cases, clopidogrel was taken 24 h before surgical intervention, either with or without prophylactic platelets, and both cases showed postoperative bleeding. There is no information about the patients’ responder status.
There is controversy regarding the decision between vaginal delivery and elective caesarean section in patients who have had an AMI. We found no convincing support for one mode of delivery over the other.
Management of AMI during pregnancy is based on a few case reports. There is still no evidence regarding optimal therapies and medications for this condition. Management of the delivery mode and anesthesia after AMI and during DAPT is highly variable, indicating a need for further information and evidence-based guidelines. The optimal strategy is yet to be determined. We should try to find clear clinical guidelines, especially as we expect a rising number of chronic ischemic heart diseases and AMI in pregnancy because of changing lifestyle factors.
Our case of a woman who had an AMI during pregnancy and received DAPT with aspirin and clopidogrel during caesarean delivery without postoperative bleeding suggests that the platelet aggregation of women on DAPT should be monitored preoperatively. This will allow clinicians to determine the correct time at which to withhold medication to minimize the risk of both stent thrombosis and peripartum bleeding.
In high-risk pregnancies, an interdisciplinary approach should be adopted, with input from obstetricians, anesthesiologists, cardiologists, neonatologists and hematologists to ensure optimal therapy and management.
Preoperative monitoring of platelet aggregation may be useful in determining the optimal point at which to withhold clopidogrel to minimize the risk of stent thrombosis and peripartum bleeding in patients receiving DAPT.
We thank Lutz Kaufner, Christina Koch, Monika Berns, Thomas Dörner and Florian Blaschke.
Conflict of interest: The authors declare no conflict of interest.
Material and Methods
Informed consent: Informed consent has been obtained from all individuals included in this study.
Ethical approval: The research related to human subject use has complied with all the relevant national regulations, and institutional policies, and is in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ institutional review board or equivalent committee.
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Accepted as E-Poster at World Congress of Perinatal Medicine, 3–6 Nov 2015, Madrid, Spain
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